The immune system is a remarkable orchestrator in the body. While it is critical in fighting off infectious pathogens, it also has the capacity to communicate with other tissues and regulate fundamental physiology. The Winer lab is interested in understanding how the immune system influences physiological processes and contributes to chronic disease. Two focuses of the lab will be to understand how the immune system contributes to insulin resistance and diabetes as a model chronic disease, and also how immunology impacts the aging process itself.
During obesity and age related insulin resistance, chronic low grade inflammation is emerging as an important factor driving the disease process. The Winer lab has made fundamental findings in understanding how the immune system, including the adaptive immune system, contributes to low grade inflammation in metabolic tissues, such as the liver and fat, as well as in the intestines during diet induced obesity. The lab also investigates how metabolic changes inside immune cells are influenced by external hormones to control immune cell function during homeostasis and disease. Thus, the focus of the lab falls into the scope of the growing field of “immunometabolism”. The goal is to use this information to develop new translational diagnostics and therapeutics, including immune therapies and vaccines.
Why it matters
The worldwide levels of obese and aged populations are at their highest amounts in human history. Obesity and aging predispose to a wide variety of chronic health issues, including insulin resistance and diabetes, which is associated with significant morbidity, mortality, and economic burden on the healthcare system. The immune system is altered during obesity and aging, and may represent a crucial common link to better understand complications of these “conditions” and to devise novel immunotherapies for them.
The immune system likely plays a role in nearly every disease, even ones previously thought to be unrelated to immunology. It is only through the study of immunology that new immunotherapies, including vaccination approaches, be available for chronic diseases and processes associated with aging or obesity.
Dan Winer, MD
Dr. Dan Winer received an Honor’s BSc in immunology from the University of Toronto, followed by an MD from the University of Ottawa in 2002. He then completed residency training in Anatomical Pathology at the University of Toronto in 2007. Subsequently, Dr. Winer did a three-year post doc in immunology at Stanford University in the laboratory of Stanford Blood Center director, Dr. Edgar Engleman. During this time, Dr. Winer, collaborating with his twin brother Dr. S. Winer at the University of Toronto, spearheaded a new initiative which identified the adaptive immune system as an important player in the control of metabolic diseases such as obesity related insulin resistance and type 2 diabetes. Dr. D. Winer returned to Canada in 2010 and became an Assistant Professor at the University of Toronto in 2011, where he ran an obesity and inflammation research lab associated with the Toronto General Research Institute (TGHRI), before joining the Buck Institute.
Dr. D. Winer is the recipient of several awards including the Hubert Wolfe Award in Endocrine Pathology, the Benjamin Castleman Award for human pathology research (sponsored by the United States and Canadian Academy of Pathology and the Massachusetts General Hospital), the Amgen early investigator award (Endocrine Society), and the Canada Research Chair in Immunometabolism.
- Tsai S, Clemente-Casares X, Zhou AC, Lei H, Ahn JJ, Chan YT, Choi O, Luck H, Woo M, Dunn SE, Engleman EG, Watts TH, Winer S and Winer DA. Insulin receptor mediated stimulation boosts T cell immunity during inflammation and infection. Cell Metabolism. 2018 Dec 4;28(6):922-934.e4.
- Ghazarian M, Revelo XS, Nøhr MK, Luck H, Zeng K, Lei H, Tsai S, Schroer SA, Park YJ, Chng MHY, Shen L, D’Angelo JA, Horton P, Chapman WC, Brockmeier D, Woo M, Engleman EG, Adeyi O, Hirano N, Jin T, Gehring AJ, Winer S, Winer DA. Type I Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome. Science Immunology. 2017 Apr 21;2(10). pii: eaai7616.
- Winer DA, Winer S, Dranse HJ, Lam TK. Immunological impact of the intestine in metabolic disease. The Journal of Clinical Investigation. 2017 Jan 3;127(1):33-42.
- Revelo XS, Ghazarian M, Chng MHY, Luck H, Kim JH, Zeng K, Shi SY, Tsai S, Lei H, Kenkel J, Liu CL, Tangsombatvisit S, Tsui H, Sima C, Xiao C, Shen L, Li X, Jin T, Lewis GF, Woo M, Utz PJ, Glogauer M, Engleman EG, Winer S, Winer DA. Nucleic Acid Targeting Pathways Promote Inflammation in Obesity Related Insulin Resistance. Cell Reports. 2016 Jul 19;16(3):717-30.
- Winer DA, Luck H, Tsai S, and Winer S. The Intestinal Immune System in Obesity and Insulin Resistance. Cell Metabolism. 2016 Mar 8;23(3):413-26.
- Luck H, Tsai S, Chung J, Clemente-Casares X, Ghazarian M, Revelo XS, Lei H, Luk CT, Shi SY, Surendra A, Copeland JK, Ahn J, Prescott D, Rasmussen BA, Chng MHY, Engleman EG, Girardin SE, Lam TK, Croitoru K, Dunn S, Philpott DJ, Guttman DS, Woo M, Winer S, Winer DA. Regulation of Obesity Related Insulin Resistance with Gut Anti-Inflammatory Agents. Cell Metabolism. 2015 Apr 7;21(4):527-42.
- Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, Engleman EG. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nature Medicine. 2011 May;17(5):610-7.
- Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM. Normalization of obesity-associated insulin resistance through immunotherapy. Nature Medicine. 2009 Aug;15(8):921-9.
Dr. Winer’s Pubmed link